What is the treatment approach for neonatal and pediatric encephalitis?

Treatment Approach for Neonatal and Pediatric Encephalitis

For suspected viral encephalitis in children, intravenous aciclovir at appropriate dosing should be started immediately without waiting for confirmatory test results, as delays beyond 48 hours significantly worsen outcomes. 1

Diagnostic Approach

Clinical Features Suggesting Encephalitis

• Constellation of current/recent febrile illness with:
  • Altered behavior, personality, cognition or consciousness
  • New onset seizures
  • New focal neurological signs 2

Initial Evaluation

1. Neuroimaging - MRI preferred over CT 2
2. Lumbar puncture for CSF analysis:
   • PCR for viral DNA (particularly HSV)
   • Cell count, protein, glucose
   • Only delay LP if significant contraindications exist (brain shift/swelling, tight basal cisterns) 2

Treatment Algorithm

Empiric Treatment

1. Initiate IV aciclovir immediately at age-appropriate dosing:

   • Children 3 months-12 years: 500 mg/m² IV every 8 hours
   • Children >12 years: 10 mg/kg IV every 8 hours 1
   • Neonates (>28 days): 20 mg/kg IV every 8 hours 1

2. Consider concurrent treatment for:

   • Bacterial meningitis if clinically indicated
   • Rickettsial or ehrlichial infection in endemic areas 2

Treatment Duration

1. For confirmed HSV encephalitis:

   • 14-21 days of IV aciclovir 2
   • Minimum of 21 days for children aged 3 months-12 years (due to higher relapse rates of 26-29%) 2

2. Consider repeat CSF examination at 14-21 days:

   • Continue treatment until CSF is negative for virus by PCR
   • Particularly important in severe disease, immunocompromised patients, or previous relapses 2

When to Stop Empiric Treatment

Aciclovir can be discontinued if:

• Alternative diagnosis is confirmed
• HSV PCR in CSF is negative on two occasions 24-48 hours apart with normal MRI
• HSV PCR in CSF is negative once >72 hours after symptom onset with normal consciousness, normal MRI, and CSF <5 × 10^6/L white cells 1

Special Considerations

Renal Monitoring

• Regular monitoring of renal function is essential
• Maintain adequate hydration to prevent aciclovir-induced nephropathy (affects up to 20% of patients, typically after 4 days of IV therapy) 2, 1
• Dose reduction necessary in patients with pre-existing renal impairment 3

Specific Viral Etiologies

1. Herpes Simplex Virus (HSV)

   • Most extensively studied with proven benefit from aciclovir 4
   • Poor prognostic factors: age >30 years, low Glasgow Coma Score (<6), symptoms >4 days before treatment, persistent confusion/aphasia/impaired consciousness >5 days 1

2. Varicella Zoster Virus (VZV)

   • Aciclovir may be effective but with less evidence than for HSV 4, 5

3. Enterovirus

   • No proven antiviral therapy
   • In children with X-linked agammaglobulinemia and enteroviral encephalitis, intraventricular γ-globulin therapy (0.2 mL/kg) via Ommaya reservoir could be considered 2

4. West Nile Virus

   • Supportive care is the mainstay of treatment
   • No proven benefit from ribavirin (potentially deleterious) 2

Autoimmune Encephalitis

For acute disseminated encephalomyelitis (ADEM):

• High-dose intravenous corticosteroids (methylprednisolone, 1g IV daily for 3-5 days) 2
• Consider plasma exchange in patients who respond poorly to corticosteroids 2

Pitfalls and Caveats

1. Avoid unnecessary testing and treatment in older children:

   • The approach used for neonates (extensive testing and empiric treatment) may not be appropriate for older children
   • In children >30 days old, HSV encephalitis is rare (0.22% positive PCR rate in one study) and typically presents with recognizable clinical features 6

2. Consider non-infectious causes:

   • Autoimmune encephalitis (particularly anti-NMDAR) is increasingly recognized as a common cause of encephalitis in children 7
   • Differential diagnosis should include metabolic, toxic, and autoimmune causes 2

3. Corticosteroid use:

   • Not routinely recommended for viral encephalitis
   • May have a role under specialist supervision for marked cerebral edema, brain shift, or raised intracranial pressure 1

4. Valaciclovir considerations:

   • Oral valaciclovir has good bioavailability and may have a role in ongoing treatment
   • Not suitable for initial treatment of encephalitis
   • Should not be used in infants <3 months due to decreased clearance 1

By following this treatment approach with prompt initiation of aciclovir and appropriate diagnostic testing, outcomes for children with encephalitis can be significantly improved, reducing mortality and long-term neurological sequelae.